DESCRIPTION, OVERALL (provided by applicant): The initial period of funding for the Functional Atlas of Nuclear Receptors has demonstrated the ability of the Consortium members to pursue the collective goal of generation and validation of high-content datasets and the distribution of these data to the wider community through a central web portal. In doing so, we greatly exceeded all of the specific aims articulated in the original application and fulfilled our mission of providing discovery-driven research datasets to the wider community with a rich data framework that provides a basis for new ideas and directions for their research. Moreover, we also demonstrated our ability to engage the wider nuclear receptor community to participate in the annotation of the resource by initiating the only active, peer reviewed, free access journal dedicated entirely to nuclear receptors (NRs). Over the four years of funding to date however, there has been an increasing emphasis placed by the sponsoring agencies involved on the need for the Consortium to establish strategies that will result in the generation and dissemination of datasets and methodologies of a more translational character. Accordingly, the scientific scope of the Consortium has shifted to reflect this emphasis. Our goals for the second phase of funding are: (1) to define the temporal and spatial physiology of NRs and to relate normal mechanisms to that of pathologic states in obesity, diabetes, cardiovascular, metabolic, toxic/environmental, senescent, oncologic, and reproductive diseases;(2) to define normal hormonal/environmental signaling to coregulator (coactivators and corepressors) complexes and to relate such signaling to the aforementioned diseases by construction of new animal models for human diseases. As in the previous funding period, we will continue to: acquire large data sets of information on NRs and coregulators that are not easily possible in R01 funded laboratories and to quickly disseminate this data world-wide to investigators in the NR/coregulator field;refine and develop new approaches to manipulate data and distribute it via the NURSA website;collect protocols, new techniques, investigative materials, animal models, and expert scientific opinions/perspectives, and provide them to the non-NURSA community for their use in laboratory/clinical investigations;and finally, we will accomplish all of the above in the context of modern genomic and proteomic technologies, and in the most cost effective and efficient manner possible.